Tsetse GmmSRPN10 Has Anti-complement Activity and Is Important for Successful Establishment of Trypanosome Infections in the Fly Midgut

Ooi, Cher-Pheng, Haines, Lee ORCID: https://orcid.org/0000-0001-8821-6479, Southern, Daniel, Lehane, Mike and Acosta Serrano, Alvaro ORCID: https://orcid.org/0000-0002-2576-7959 (2015) 'Tsetse GmmSRPN10 Has Anti-complement Activity and Is Important for Successful Establishment of Trypanosome Infections in the Fly Midgut'. PLoS Neglected Tropical Diseases, Vol 9, Issue 1, e3448.

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Abstract

The complement cascade in mammalian blood can damage the alimentary tract of haematophagous arthropods. As such, these animals have evolved their own repertoire of complement-inactivating factors, which are inadvertently exploited by blood-borne pathogens to escape complement lysis. Unlike the bloodstream stages, the procyclic (insect) stage of Trypanosoma brucei is highly susceptible to complement killing, which is puzzling considering that a tsetse takes a bloodmeal every 2–4 days. In this study, we identified four tsetse (Glossina morsitans morsitans) serine protease inhibitors (serpins) from a midgut expressed sequence tag (EST) library (GmmSRPN3, GmmSRPN5, GmmSRPN9 and GmmSRPN10) and investigated their role in modulating the establishment of a T. brucei infection in the midgut. Although not having evolved in a common blood-feeding ancestor, all four serpins have an active site sharing remarkable homology with the human complement C1-inhibitor serpin, SerpinG1. RNAi knockdown of individual GmmSRPN9 and GmmSRPN10 genes resulted in a significant decreased rate of infection by procyclic form T. brucei. Furthermore, recombinant GmmSRPN10 was both able to inhibit the activity of human complement-cascade serine proteases, C1s and Factor D, and to protect the in vitro killing of procyclic trypanosomes when incubated with complement-activated human serum. Thus, the secretion of serpins, which may be part of a bloodmeal complement inactivation system in tsetse, is used by procyclic trypanosomes to evade an influx of fresh trypanolytic complement with each bloodmeal. This highlights another facet of the complicated relationship between T. brucei and its tsetse vector, where the parasite takes advantage of tsetse physiology to further its chances of propagation and transmission.

Item Type:	Article
Subjects:	QU Biochemistry > Enzymes > QU 143 Enzyme inhibitors QX Parasitology > Insects. Other Parasites > QX 505 Diptera QX Parasitology > Protozoa > QX 70 Mastigophora. (e.g., Giardia. Trichomonas. Trypanosoma. Leishmania) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 705 Trypanosomiasis
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pntd.0003448
Depositing User:	Carmel Bates
Date Deposited:	04 Feb 2015 10:29
Last Modified:	27 Sep 2019 15:29
URI:	https://archive.lstmed.ac.uk/id/eprint/4842

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